Nociceptin/orphanin FQ (N/OFQ) is a 17-residue neuropeptide that binds the nociceptin opioid-like receptor (NOP). N/OFQ exhibits nucleotidic and aminoacidics sequence homology with the precursors of other opioid neuropeptides but it does not activate either MOP, KOP or DOP receptors. Furthermore, opioid neuropeptides do not activate the NOP receptor. Generally, activation of N/OFQ system exerts anti-opioids effects, for instance toward opioid-induced reward and analgesia. The NOP receptor is widely expressed throughout the brain, whereas N/OFQ localization is confined to brain nuclei that are involved in stress response such as amygdala, BNST and hypothalamus. Decades of studies have delineated the biological role of this system demonstrating its involvement in significant physiological processes such as pain, learning and memory, anxiety, depression, feeding, drug and alcohol dependence. This review discusses the role of this peptidergic system in the modulation of stress and stress-associated psychiatric disorders in particular drug addiction, mood, anxiety and food-related associated-disorders. Emerging preclinical evidence suggests that both NOP agonists and antagonists may represent a effective therapeutic approaches for substances use disorder. Moreover, the current literature suggests that NOP antagonists can be useful to treat depression and feeding-related diseases, such as obesity and binge eating behavior, whereas the activation of NOP receptor by agonists could be a promising tool for anxiety.

Role of Nociceptin/Orphanin FQ-NOP Receptor System in the Regulation of Stress-Related Disorders

Socioeconomic disadvantage may be a significant risk factor for disordered eating, particularly for individuals with underlying genetic risk. However, little to nothing is known about the impact of disadvantage on disordered eating in boys during the critical developmental risk period. Crucially, risk models developed for girls may not necessarily apply to boys, as boys show different developmental patterns of disordered eating risk (i.e., earlier activation of genetic influences during adrenarche, an early stage of puberty). This is the first study to examine phenotypic and Genotype × Environment (G × E) effects of disadvantage in boys. Analyses examined 3,484 male twins ages 8-17 (Mage = 12.27, SD = 2.96) from the Michigan State University Twin Registry. Disordered eating (e.g., body dissatisfaction, binge eating) was measured using the parent-report Michigan Twins Project Eating Disorder Survey. Neighborhood disadvantage was measured using a census-tract level Area Deprivation Index, and family socioeconomic status was determined from parental income and education. Adrenarche status was determined using multiple indicators, including age and Pubertal Development Scale scores. G × E models suggested that genetic influences on disordered eating were activated earlier for boys experiencing familial or neighborhood disadvantage, with substantial genetic influences in early adrenarche, when genetic influences were low in more advantaged boys. Phenotypically, both neighborhood and familial disadvantage were associated with greater disordered eating for boys in late adrenarche, which could indicate a lasting impact of earlier activation of genetic influences on later risk. Results highlight disadvantage as a novel risk factor for disordered eating in boys, particularly those with genetic vulnerabilities. (PsycInfo Database Record (c) 2023 APA, all rights reserved). 

Disadvantage and disordered eating in boys: Examining phenotypic and genotype × environment associations across development.

Eating disorders (EDs) have long been considered conditions exclusively affecting women, and studies in the ED field regularly exclude men. Research efforts are needed to better understand the role of gender and sex in EDs. This review describes the role of gender and sex in the development of EDs from a biopsychosocial perspective.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/brb3.2871

Gender and sex in eating disorders: A narrative review of the current state of knowledge, research gaps, and recommendations

Binge Eating Risk During Midlife and the Menopausal Transition: Sensitivity to Ovarian Hormones as Potential Mechanisms of Risk

Abstract Background Binge eating disorder (BED) is a pernicious psychiatric disorder which is linked with broad medical and psychiatric morbidity, and obesity. While BED may be characterized by altered cortical morphometry, no evidence to date examined possible sex-differences in regional gray matter characteristics among those with BED. This is especially important to consider in children, where BED symptoms often emerge coincident with rapid gray matter maturation. Methods Pre-adolescent, 9–10-year old boys ( N = 38) and girls ( N = 33) with BED were extracted from the 3.0 baseline (Year 0) release of the Adolescent Brain Cognitive Development Study. We investigated sex differences in gray matter density (GMD) via voxel-based morphometry. Control sex differences were also assessed in age and body mass index and developmentally matched control children (boys N = 36; girls N = 38). Among children with BED, we additionally assessed the association between dorsolateral prefrontal (dlPFC) GMD and parent-reported behavioral approach and inhibition tendencies. Results Girls with BED uniquely demonstrate diffuse clusters of greater GMD ( p &lt; 0.05, Threshold Free Cluster Enhancement corrected) in the (i) left dlPFC ( p = 0.003), (ii) bilateral dmPFC ( p = 0.004), (iii) bilateral primary motor and somatosensory cortex ( p = 0.0003) and (iv) bilateral precuneus ( p = 0.007). Brain-behavioral associations suggest a unique negative correlation between GMD in the left dlPFC and behavioral approach tendencies among girls with BED. Conclusions Early-onset BED may be characterized by regional sex differences in terms of its underlying gray matter morphometry. 

Sex differences in regional gray matter density in pre-adolescent binge eating disorder: a voxel-based morphometry study

Binge eating is a transdiagnostic symptom that disproportionately affects females. Sexually dimorphic gonadal hormones (e.g., estradiol, testosterone) substantially impact eating behavior and may contribute to sex differences in binge eating. We examine recent evidence for the role of gonadal hormones in binge eating risk across development. Both organizational (long-lasting impact on the central nervous system (CNS)) and activational (transient influences on the CNS) hormone effects may contribute to sex differences in binge eating. Gonadal hormones also impact within-sex variability in binge eating, with higher estradiol levels in females and higher testosterone levels in males protective across development. Emerging evidence suggests that the impact of gonadal hormones may be greatest for people with other risk factors, including genetic, temperamental (e.g., high negative affect), and psychosocial (e.g., exposure to weight-based teasing) risk. Gonadal hormones contribute to sex differences and within-sex variability in binge eating across development.

Carolina Anaya

Papers

Gonadal Hormone Influences on Sex Differences in Binge Eating Across Development